The present invention relates to packaging for transdermal/transmucosal drug delivery patches.
Transdermal and transmucosal patches containing drugs such as estradiol, levonorgestrel, testosterone, scopolamine, nitroglycerin, nicotine, heparin, melatonin, diagnostic compounds, and other ingredients are conventionally required to be packaged in hermetically sealed, individual foil and/or plastic pouches. Such packaging is necessary in order to maintain sanitary conditions and to prevent degradation, contamination, and/or loss of sensitive ingredients by environmental exposure. In many cases, the material used for such packaging has to be sufficiently impervious to volatile active ingredients, e.g., nitroglycerin, and environmental factors, e.g., humidity, to allow the device to remain stable under extended storage conditions of up to several years.
A serious disadvantage of conventional packaging is that the user must tear open a separate pouch each time one of the transdermal or transmucosal patches is needed. Furthermore, it is desirable for many pharmaceutical products that the packaging material be difficult to open by children, so called xe2x80x9cchild-resistantxe2x80x9d packaging. These conventional pouches may not be child-resistant, but can be difficult to open, particularly for the elderly and those with conditions that impair strength and/or manual dexterity, and especially if the packaging is made of tear resistant or hard to grasp materials. Even for those without any special difficulties, opening such pouches on a frequent basis over an extended period can be a substantial inconvenience. Moreover, individual packaging can be expensive and wasteful due to the excessive packaging material required and manufacturing cost for individual packaging.
It would be desirable to package transdermal and transmucosal drug-containing patches so as to be simple to open for adult patients, difficult for children to open, economical, sufficiently impervious to prevent loss of volatile components, and easy to manufacture.
The present invention provides a dispenser for conveniently dispensing multiple transdermal/transmucosal drug-containing patches from a single container. The dispenser has a separate inner cartridge having walls made of an impermeable material, wherein the inner cartridge is hermetically sealed during storage. A plurality of individual patches are contained within the inner cartridge, and the patches can be removed from the dispenser through at least one aperture. The dispenser further comprises a housing comprising a base and an exterior cover, wherein the housing is adapted to fully enclose the inner cartridge and is capable of forming an impermeable seal defining an outer chamber.
In one preferred embodiment, the aperture of the inner cartridge is sealed with a foil seal, such that the inner cartridge is hermetically sealed during storage. The seal is then opened, broken, or otherwise removed in order to allow the enclosed transdermal patches to be removed from the inner cartridge during use. The inner cartridge is enclosed by a housing having a base and an exterior cover.
Preferably, the aperture has a secondary seal, such as a plastic film with a slit in the middle, or overlapping plastic films, which allows the patches to be removed, but otherwise minimizes air transfer into the inner cartridge and serves as a barrier for foreign debris.
In use, the inner cartridge is contained within the housing that contains other functional portions of the dispenser, such as a cover, buttons or other opening mechanisms, as well as defining the cosmetic appearance of the dispenser.
One benefit of this embodiment is the ability to improve stability, since the inner cartridge is the primary stability container closure during shelf life. The housing only has to maintain stability of the transdermal patch from the time that the inner cartridge seal is removed until the transdermal patches are exhausted from the dispenser. Separation of the inner cartridge and housing functions allows greater design flexibility for the housing, since cosmetic changes can be made to the housing with little or no impact on the pharmaceutical stability. Separation of the inner cartridge and housing functionality also provides the ability to make manufacturing processes more efficient and low cost, as well as providing for more convenient means of allowing the dispenser to be refillable.
In another aspect, the present invention provides a cartridge for use in a transdermal/transmucosal patch dispenser. The inner cartridge has walls made of an impermeable material, wherein the inner cartridge is hermetically sealed during storage. A plurality of individual patches is contained within the inner cartridge, and the patches can be removed from the cartridge through at least one aperture. The cartridge is adapted to be enclosed by a housing comprising a base and an exterior cover, wherein the housing is capable of forming an impermeable seal defining an outer chamber.
In yet another aspect, the present invention provides a dispenser for conveniently dispensing multiple transdermal/transmucosal drug-containing patches from a single container, wherein a child-resistant mechanism is incorporated into the dispenser. The dispenser has an inner cartridge defined by walls made of an impermeable material, wherein the inner cartridge is hermetically sealed during storage. A plurality of individual patches is contained within the inner cartridge, and the patches can be removed from the dispenser through at least one aperture. The dispenser further comprises an exterior cover adapted to enclose the aperture when the exterior cover is in a closed position.
The child-resistant mechanism can consist of a locking mechanism, a xe2x80x9clock-outxe2x80x9d mechanism, an opening mechanism not readily apparent to children or not readily engaged by children, or any combination of the above. Locking mechanisms may include, for example, keypad or combination locks, keyed locks, or locks activated by biometric identification, such as through use of fingerprints. A xe2x80x9clock-outxe2x80x9d mechanism may, for example, need to be activated by a magnetic or radio frequency identification signal before allowing the mechanism to open. Preferably, one or more triggering mechanisms, such as buttons, latches, levers, and the like, would have to be appropriately engaged before the dispenser could be opened for dispensing medicine. A xe2x80x9cgravity switchxe2x80x9d (i.e., a switch, latch, lock, or similar mechanism having gravity dependent operability related to physical orientation) could be employed, wherein engagement of the triggering mechanism allows the dispenser to open only if the dispenser is held in a particular, fixed orientation, such as parallel to the ground. Placing the dispenser in the proper alignment with relation to the ground, such that the gravity switch allows the dispenser to open, can be described as xe2x80x9cengagingxe2x80x9d the gravity switch.
In a particularly preferred embodiment, the dispenser is opened by activating a button while the dispenser is aligned such that a gravity switch is engaged.
In another particularly preferred embodiment, the dispenser is opened by simultaneously activating two (or more) buttons while the dispenser is aligned such that the gravity switch is engaged.
One benefit of this invention is to reduce the likelihood of a non-user being accidentally exposed to the active pharmaceutical ingredients in a transdermal/transmucosal patch. Additionally, embodiments with locking mechanisms can be used to deter abuse of the transdermal patches and xe2x80x9clock-outxe2x80x9d mechanisms can be used to prevent patients from dosing with too many patches at one time. In a preferred embodiment, the dispenser has a lock-out mechanism and contains a controlled substance (e.g., a substance regulated in the United States by the Drug Enforcement agency), such as morphine, fentanyl, buprenorphine, or testosterone.
The transdermal/transmucosal patches are preferably arranged such that the removal of one patch thereby allows the next patch to be grasped and removed, and more preferably the patches are separably interconnected together such that the action of removing one of the transdermal/transmucosal patches thereby moves another patch into position for subsequent removal.
In a particularly preferred embodiment, the dispenser walls defining the inner cartridge are made of rigid plastic and the aperture is in the form of a single slot through which each of the transdermal/transmucosal patches is pulled. Each patch is preferably separably interconnected to an adjacent patch so that pulling one patch out of the slot pulls a portion of the next patch through the slot and into position for subsequent grasping and removal. The separable interconnection of the patches is preferably accomplished in one of essentially three ways:
(1) via a continuous release liner upon which the individual transdermal/transmucosal patches are commonly adhered, in which case the liner is preferably perforated between each patch to facilitate separation, (2) without a continuous release liner, but where there is either an added portion of adhesive between the release liner and backing of successive patches or where a part of the adhesive underside of one patch is directly adhered to a portion of the top surface of the next patch to be dispensed, or (3) without a continuous release liner, but where a portion of each patch is interleaved beneath a portion of the next patch to be dispensed.
The patches, which generally are not individually packaged, may be folded, stacked, and/or interleaved together one on top of another within the cartridge so that a large number of patches can be stored efficiently in a small space.
Alternatively, the individual transdermal/transmucosal patches may not be folded, stacked, and/or interleaved on top of each other, but instead arranged sequentially on a roll, or on a flat strip or continuous loop arrangement. In this case, depending on the design, the dispenser may have either a single aperture or multiple apertures (one for each patch). Also, the aperture may include a resilient sealing member to help prevent escape of volatile components and/or environmental contamination of the transdermal/transmucosal patch-containing cartridge.
Moreover, the dispenser may contain additional features, such as a desiccant, a moisture exposure indicator strip, a ratcheting mechanism, or a counter mechanism as described in copending U.S. patent application Ser. No. 08/982,813 (Richard G. Sitz et al.), the disclosure of which is incorporated herein by reference.
Preferred drug-containing transdermal/transmucosal patches to be dispensed from a dispenser according to the present invention are those which are administered on a weekly, twice-weekly, or daily basis, such as hormone replacement therapy and fertility control patches containing, for example, estradiol, progestins, and/or testosterone. Other examples of preferred patches include frequently applied patches such as nitroglycerin, nicotine, and fentanyl.
Finally, the present invention also provides a method of packaging transdermal/transmucosal drug-containing patches for convenient dispensing, comprising the steps of (i) providing a dispenser unit having walls defining an inner cartridge, an aperture, and a housing adapted to fully enclose the inner cartridge, and (ii) packaging a plurality of transdermal/transmucosal drug-containing patches within the inner cartridge and, preferably, arranging the patches so as to allow (and preferably require) removal of one patch at a time in a predetermined sequential order through the aperture.